Osteopontin mediated eosinophils activation by group II innate lymphoid cells

Abstract

Background: Osteopontin (OPN) can regulate Th2 inflammation in allergic rhinitis (AR). A recent study suggested that group II innate lymphoid cells (ILC2s) were very important for airway inflammation. But the role of OPN in ILC2s regulation is not explored. Methods: Purified ILC2s were stimulated by human recombinant OPN. The expression of GATA3 and RORα was assayed using real-time polymerase chain reaction (PCR) and enzyme linked immunosorbent assay. MiR-181a was transfected into eosinophils to test the OPN production. The protein concentrations of interleukin (IL)-5 and IL-13 were examined using ELISA. Purified eosinophils and ILC2s were cocultured and stimulated by OPN and the activation of eosinophils was detected by ELISA. Results: After OPN stimulation, the ILC2s proliferation, the mRNA levels of GATA3 and RORα, the protein of GATA3, RORα, IL-5 and IL-13 expression were up-regulated significantly in a dose dependent manner. Eosinophils cultured alone transfected with miR-181a mimics produced less OPN protein compared with eosinophils transfected with miR-control, whereas OPN production was significantly promoted when miR-181a inhibitor was transfected. In the eosinophils and ILC2s coculture system, eosinophil cationic protein (ECP) production induced by OPN or IL-33 were significantly higher than ECP production in eosinophils culture system. OPN presented similar potency with IL-33 in the activation of eosinophils. When anti-IL-5 antibody was added, the production of ECP was significantly inhibited. Conclusions: Our data for the first time provided new evidence that OPN played important roles in innate immunity of AR by regulation of ILC2s and the interaction between ILC2s and eosinophils.

Keywords

• Osteopontin
• Allergic rhinitis
• Group II innate Lymphoid cells
• Eosinophils